Table 1.
Inheritance patterns of variants with wild-type-like or recessive functional features
| Variant | Functional | Clinical/Genetic | Sum | Location | ||||
|---|---|---|---|---|---|---|---|---|
| Dominant | Sporadic | Recessive | Uncertain | Unknown | ||||
| p.His29Pro | Wild-type-like | – | – | 1 | – | – | 1 | IC |
| p.Ser70Leu | Wild-type-like | – | – | 1 | – | – | 1 | IC |
| p.Arg105Cys | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| p.Leu106Val* | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| p.Gln154Arg | Wild-type-like | – | – | – | 1 | – | 1 | TM1 |
| p.Gly222Ser | Wild-type-like | – | – | – | 1 | – | 1 | TM1 |
| p.Val327Ile | Wild-type-like | – | – | – | – | 2 | 2 | TM1 |
| p.Ala331Ser* | Wild-type-like | – | – | 1 | – | – | 1 | TM1 |
| p.Phe333Leu* | Wild-type-like | – | – | 1 | – | – | 1 | TM1 |
| p.Ala402Val | Wild-type-like | – | 1 | 1 | – | – | 2 | TM2 |
| p.Pro408Ala | Wild-type-like | – | – | 2 | 1 | 3 | 6 | TM2 |
| p.Val456Ile* | Wild-type-like | – | – | – | – | 1 | 1 | TM2 |
| p.Ala493Thr* | Wild-type-like | – | – | – | – | 1 | 1 | TM2 |
| p.Phe494Leu* | Wild-type-like | – | – | – | 1 | – | 1 | TM2 |
| p.Leu587Val* | Wild-type-like | – | – | 2 | – | – | 2 | IC |
| p.Gly594Val* | Wild-type-like | – | – | – | – | 1 | 1 | IC |
| p.Arg611His* | Wild-type-like | – | – | – | 1 | 1 | 2 | IC |
| p.Met646Thr* | Wild-type-like | – | – | 1 | – | – | 1 | IC |
| p.His664Pro* | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| p.Arg669Cys | Wild-type-like | – | 1 | – | – | – | 1 | IC |
| p.Gly688Arg* | Wild-type-like | – | – | – | – | 1 | 1 | IC |
| p.Pro744Thr | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| p.Thr837Ile* | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| p.Val851Met | Wild-type-like | – | – | 2 | – | −. | 2 | IC |
| p.Gly898Arg* | Wild-type-like | – | – | – | 1 | – | 1 | IC |
| Total | Wild-type-like | - | 2 | 12 | 11 | 10 | 35 | |
| p.Phe167Leu | Recessivea | – | – | 7 | 4 | 2 | 13 | TM1 |
| p.Gly190Arg | Recessiveb | – | – | 3 | 1 | – | 4 | TM1 |
| p.Leu198Val | Recessivea | – | – | – | 1 | – | 1 | TM1 |
| p.Ala221Glu* | Recessiveb | – | – | 1 | – | – | 1 | TM1 |
| p.Gly233Ser | Recessiveb | – | – | 1 | – | – | 1 | TM1 |
| p.Val273Met | Recessivea | – | – | – | – | 1 | 1 | TM1 |
| p.Gly276Ser | Recessivea | – | – | 1 | – | – | 1 | TM1 |
| p.Cys277Arg | Recessiveb | – | – | 1 | – | – | 1 | TM1 |
| p.Gly285Val* | Recessiveb | 1 | – | – | – | – | 1 | TM1 |
| p.Glu291Lys | Recessiveb | – | – | 1 | – | – | 1 | TM1 |
| p.Arg317Leu | Recessivea | – | – | 1 | – | – | 1 | TM1 |
| p.Ala320Val | Recessivea | – | – | 1 | – | – | 1 | TM1 |
| p.Arg338Gln | Recessivea | – | – | 1 | – | 1 | 2 | TM1 |
| p.Gly355Arg | Recessiveb | – | – | 1 | – | – | 1 | TM2 |
| p.His369Pro | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Val397Asp* | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Phe413Cys | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Glu422Lys | Recessiveb | – | – | – | 1 | – | 1 | TM2 |
| p.Trp433Arg | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Phe463Ile* | Recessiveb | – | – | 1 | – | – | 1 | TM2 |
| p.Gly483Ser* | Recessivea | – | – | 1 | – | – | 1 | TM2 |
| p.Met485Val | Recessiveb | – | – | 6 | 4 | 1 | 11 | TM2 |
| p.Ala493Glu | Recessiveb | – | – | 1 | – | – | 1 | TM2 |
| p.Glu500Lys* | Recessiveb | – | – | 1 | – | – | 1 | TM2 |
| p.Pro521Thr* | Recessiveb | – | – | 1 | – | – | 1 | TM2 |
| p.Ala529Val* | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Glu548Lys | Recessiveb | – | – | – | – | 1 | 1 | TM2 |
| p.Thr550Met | Recessiveb | – | – | – | 1 | – | 1 | TM2 |
| p.Pro558Ser | Recessiveb | – | – | 2 | – | – | 2 | TM2 |
| p.Met560Thr | Recessivea | – | – | – | – | 1 | 1 | TM2 |
| p.Ala566Thr | Recessiveb | – | – | 2 | – | – | 2 | TM2 |
| p.Gln583Arg* | Recessivea | – | – | 1 | – | 1 | 2 | TM2 |
| p.Val640Phe* | Recessiveb | – | – | 1 | – | – | 1 | IC |
| p.Asp822Asn* | Recessivea | – | – | 1 | – | – | 1 | IC |
| p.Pro883Thr | Recessivea | – | – | 1 | – | 2 | 3 | IC |
| Total | Recessive | 1 | - | 38 | 12 | 15 | 66 | |
Asterisks following variant name indicate variants not reported in the literature previously. Functional = classification according to functional feature; Clinical/Genetic = number of pedigrees with distinct inheritance patterns of clinical symptoms. Location = if the variant is found in intracellular domain (IC: residues 1–110, 586–988), first (TM1: residues 111–344) or second (TM2: residues 345–585) of the transmembrane repeats. Data for the variants that were not missense are presented in Supplementary Table 3.
For recessive variants it is specified if the variant in homomeric condition expresses currents with shifted voltage dependence of activationa or reduced current amplitudeb.